From a neurobiological and ethological perspective, human language exists on a substrate of sensory and motor processes. The anatomical basis of language in the perisylvian cortex rests at the crossroads of auditory, visual, somatosensory, and motor cortices, and the physiology of language incorporates multimodal processing across all of these domains. However, only the motor system has the capability of action, and as a result, this system has been implicated in many cognitive functions that require either explicit or implicit action. An important source of information for language comprehension comes from the perception of action, including the movements of the mouth and hands. The neural interactions involved in processing this information involve the premotor cortex, the inferior parietal lobule, and the superior temporal gyrus. These regions and the neural connections among them comprise a human system for observation-execution matching that appears to have a phylogenetic basis in the "mirror neuron" system of the macaque. It appears that this system operates by covert simulation of perceived action. Such simulation, or analysis- by-synthesis, may also play a role in other language tasks, such as syntactic processing. In fact, there is substantial evidence that dysgranular premotor regions of the cerebral cortex, particularly the posterior part of the left inferior frontal gyrus and adjacent regions, play a major role in the structural aspects of sentence processing. Finally, motor cortices also appear to play a role in representing the meaning of action-related sentences, and this too has been thought to involve motor imagery and/or covert simulation. We propose to use functional magnetic resonance imaging (fMRI) to dissect out the roles of the motor cortices, cortico-cortical interactions, and motor simulation in language comprehension. In the present application, we test the hypotheses that (1) action understanding aids phonological disambiguation across environmental and contextual variation through covert motor simulation of perceived articulatory movements; (2) comprehension of symbolic gestures involves a direct visual semantic mechanism, not involving simulation, whereas speech-associated gesture involves observation-execution matching; (3) analysis-by-synthesis only plays a role in normal sentence processing when pure analysis does not succeed; (4) the context and communicative goals of action-related sentences can fundamentally affect the role of motor simulation in encoding their meaning; and (5) unilateral premotor injury impairs action understanding for speech perception, and that compensation by contra-lesional circuits correlates with residual ability. The five experiments proposed here aim to characterize the neural mechanisms of situated and embodied language comprehension, and to elaborate further the role of the motor cortices in language. PUBLIC HEALTH RELEVANCE The neural mechanisms of language comprehension are finally being elucidated, thanks to technological breakthroughs of the past decade that permit a robust human brain physiology. By understanding the normal physiology of language, we are hopeful that we will gain insight into the nature of injury to the language system and the mechanisms of neural repair relevant for language recovery. [unreadable] [unreadable] [unreadable] [unreadable]